Synthesis and biological evaluation of vinyl ether-containing azole derivatives as inhibitors of Trichophyton rubrum

In an attempt to search for many target compounds with excellent activities, a series of vinyl ether-containing azole derivatives were designed, synthesized, and evaluated as antifungal agents. Results of preliminary antifungal tests against Trichophyton rubrum in vitro indicated that most of the synthesized compounds showed excellent activities. In comparison with fluconazole, itraconazole, voriconazole, omoconazole and amphotericin B, several compounds (such as 7d, 7g and 7h) exhibited more potent inhibitory activities, suggesting that they were promising leads for the development of novel antifungal agents.     

Synthesis and antimicrobial activity of new 3 alpha-hydroxy-23,24-bisnorcholane polyamine carbamates.

3 alpha-Hydroxy-23,24-bisnorcholane spermidine and spermine carbamates 2-7 have been synthesized and their antimicrobial and hemolytic activities were evaluated. They exhibited excellent in vitro activities especially against methicillin-resistant Staphylococcus aureus.     

Synthesis and antibacterial activity of 7-(substituted)aminomethyl quinolones

A series of 7-(substituted)aminomethyl quinolones was synthesized and evaluated for antibacterial activity. Derivatives with (monoalkyl)aminomethyl substituent at C-7 displayed high in vitro activities comparable to Lomefloxacin against gram-negative organisms, whereas those bearing a [(substituted)phenyl]aminomethyl side chain at C-7 demonstrated good activities against gram-positive organisms as potent as Lomefloxacin and Vancomycin.     

Synthesis of 13-(substituted benzyl) berberine and berberrubine derivatives as antifungal agents

By introducing various aromatic groups in 13-C of berberine and berberrubine, a series of 13-(substituted benzyl) berberine and berberrubine derivatives were synthesized and examined for antifungal activities against various human pathogenic fungi. The synthesized compounds exhibited more potent antifungal activities than berberine and berberrubine. Among them, 13-(4-isopropyl benzyl) berberine (6e) exerted the most potent antifungal activities against Candida species (MIC=1-8 microg/ml) and a 4-fold stronger activity than 13-(4-isopropyl benzyl) berberrubine (7e) synthesized by pyrolysis of compound 6e.     

Synthesis and biological activity of 4',8-dihydroxyisoflavon-7-yl D-hexopyranosides

Four 4',8-dihydroxyisoflavon-7-yl hexopyranoside derivatives having an aglycon part of A-76202 were synthesized, and their biological activities were evaluated toward rat liver alpha-glucosidase. However, the activities were disappointing.     

An efficient synthesis of highly functionalized novel chromeno[4,3-b]pyrroles and indolizino[6,7-b]indoles as potent antimicrobial and antioxidant agents

A facile and efficient synthesis of novel chromeno[4,3-b]pyrroles has been accomplished by intramolecular 1,3-dipolar cycloaddition which on subsequent Pictet-Spengler cyclisation in presence of p-toluenesulfonic acid yielded indolizino[6,7-b]indoles. The synthesized chromenopyrroles and indolizinoindoles were evaluated for their antimicrobial and antioxidant activities. Compounds 7b, 7e, 7a and 7d exhibited respectively, good antibacterial and antifungal activities against tested pathogens when compared to reference control.     

Synthesis and evaluation of azaindole-alpha-alkyloxyphenylpropionic acid analogues as PPARalpha/gamma agonists

A series of azaindole-alpha-alkyloxyphenylpropionic acid analogues was synthesized and evaluated for PPAR agonist activities. Structure-activity relationship was developed for PPARalpha/gamma dual agonism. One of the synthesized compound 7a was identified as a potent, selective PPARalpha/gamma dual agonist.     

Docking and 3-D QSAR studies of dual PDE4-PDE7 inhibitors†

Small dual-specificity molecules inhibiting PDE4 and PDE7 can be used to treat inflammatory diseases. To design and synthesize dual PDE4 and PDE7 inhibitors, we carried out the target-based docking and the 3D QSAR study using CoMFA. Three compounds were synthesized. We predicted their inhibitory activities using our 3D QSAR model and tested their activities against PDE4 and PDE7 in vitro.     

Synthesis and cytotoxic activities of 6-chloro-7-arylamino-5,8-isoquinolinediones.

6-Chloro-7-arylamino-5,8-isoquinolinediones were newly synthesized and evaluated for in vitro cytotoxic activities against five human solid tumor cell lines. Among them, 5b, 5c and 5d exhibited potent activities against the cell lines HCT-15 and SK-MEL-2.     

Anticancer activities of some newly synthesized pyridine, pyrane, and pyrimidine derivatives

A series of pyridine, pyrane, and pyrimidine derivatives (2-11) were newly synthesized using nitrobenzosuberone 1 as a starting material. The antitumor activities of the synthesized compounds were evaluated utilizing 59 different human tumor cell lines, representing leukemia, melanoma, lung, colon, brain, ovary, breast, prostate as well as kidney. Some of the tested compounds especially 2, 3, 4c, 6, 7, 9b, 10a, and 11 exhibited better in vitro antitumor activities at low concentration (log(10) GI(50) = -4.7) against the used human tumor cell lines. Additionally, compounds 3, 4c, 6, 7, and 9b were highly selective to inhibit leukemia cell lines. The detailed synthesis, spectroscopic data and antitumor properties for the synthesized compounds were reported.     

Structure-activity relationships of 6-fluoroquinazolines: dual-acting compounds with inhibitory activities toward both TNF-alpha production and T cell proliferation

We synthesized various 6-fluoro-7-(1-piperazino)quinazolines based on the structure of 1 and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses. Among these compounds, 7a, having the 3,4-(methylenedioxy)phenyl moiety at the C(4)-position of the quinazoline ring, showed both inhibitory activities. Furthermore, the oral treatment with 7a exhibited an anti-inflammatory effect in rats with adjuvant arthritis as well as an inhibitory activity toward LPS-induced TNF-alpha production.     

Hypocholesterolemic activity of hesperetin derivatives

Hesperetin ester and ether derivatives possessing a long alkyl chain were synthesized for examining their hypocholesterolemic activities in high cholesterol-fed mice. Hesperetin 7-O-lauryl ether (4b) and hesperetin 7-O-oleyl ether (4e) exhibited strong cholesterol-lowering effects.     

Synthesis of 7-chloro-5-trifluoromethyl/7-fluoro/7-trifluoromethyl-4H-1,4-benzothiazines as antimicrobial agents

7-Chloro-5-trifluoromethyl/7-fluoro/7-trifluoromethyl-4H-1,4-benzothiazines have been synthesized by 2-amino-5-fluoro/5-trifluoromethyl/5-chloro-3-trifluoromethyl benzenethiols condensed with beta-diketone/beta-ketoesters in the presence of DMSO involving oxidative cyclization. Pharmacological activities have also been included.     

Synthesis of 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives and their screening for antimicrobial and antioxidant properties

Novel 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives have been synthesized using boron trifluoride diethyl etherate catalyzed Diels–Alder reaction. This method presents considerable synthetic advantages in terms of high atom economy, mild reaction condition and good yields. The synthesized compounds have been screened for their antibacterial and antioxidant activities.     

Synthesis and structure-activity relationship of 7-(substituted)-aminomethyl-4-quinolone-3-carboxylic acid derivatives

Gram-positive organisms have re-emerged as the major hospital pathogens, which make the unmet medical needs for antibacterial therapy even worse. In searching for potent agents against Gram-positive pathogens, novel 7-(substituted)-aminomethyl-quinolone-3-carboxylic acids were designed, synthesized, and evaluated for their antibacterial activities in vitro. Many 7-monoarylaminomethyl derivatives exhibited high potency against Gram-positive organisms compared to reference agents: vancomycin and pazufloxacin. Additionally, a few 7-monoalkylaminomethyl derivatives exhibited good activities against both Gram-positive and Gram-negative organisms.     

Synthesis and anti-HIV activity of unusual nucleoside oxanosine derivatives.

A series of the oxanosine and carbocyclic oxanosine derivatives were synthesized to evaluate for their anti-HIV activity. Compound 1, 7 and 9 showed weak anti-HIV activities.     

Synthesis and anti-tumor evaluation of new trisulfide derivatives

New bis-aromatic and heterocyclic trisulfide derivatives 5, 7-10 were synthesized by optimizing lead dibenzyl trisulfide natural product (4) to evaluate their anti-tumor activities. Five compounds 5-7, 9, and 10 exhibited potent anti-tumor activities against eight different tumor cell lines with low cytotoxicity against HepG2. Initial SAR was discussed, and MOA of these anti-microtubule agents was suggested based on cell kinetic response patterns observed on RT-CES system.     

Synthesis,in vitro antimicrobial and cytotoxic activities of novel pyrimidine–benzimidazol combinations

A series of novel 4-substituted-2-{[(1H-benzo[d]imidazol-2-yl)methyl] thio}-6-methylpyrimidine derivatives were designed, synthesized and evaluated for their cytotoxic activities against four human cancer cell lines and inhibitory activities against five type culture strains in vitro. Some of synthetic pyrimidine–benzimidazol combinations showed good inhibitory activities against Stenotrophomonas maltophilia, especially compounds 7b and 7c. Compounds 7a and 7d exhibited enhanced activities against MGC-803 in vitro, when compared to 5-Fu.     

Synthesis,anti-inflammatory,analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives

Design, synthesis and pharmacological activities of a group of 1,3,5-trisubstituted pyrazolines were reported. The chemical structures of the synthesized compounds have been assigned on the basis of IR, MS, ¹H NMR, and ¹³C NMR spectral analyses. The synthesized 1,3,5-trisubstituted pyrazoline derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 4h, 6e, 7a, 7e, and 9 showed more potent anti-inflammatory and analgesic activities than the reference drug celecoxib. On the basis of their higher activities in the in vivo studies compared with celecoxib, the five compounds 4h, 6e, 7a, 7e and 9 were selected to test their inhibitory activities against ovine COX-1/2 using an in vitro cyclooxygenase inhibition assay. Docking study of compounds 7a, 7e and 9 into the COX-2 binding site revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.